Romano Ryan C, Shon Wonwoo, Sukov William R
Mayo Clinic, Rochester, MN, USA.
Mayo Clinic, Rochester, MN, USA
Int J Surg Pathol. 2016 Sep;24(6):512-8. doi: 10.1177/1066896916648379. Epub 2016 May 15.
Background Malignant melanoma of the nail apparatus is exceedingly rare. Increasingly, genetic studies have been employed to aid in distinguishing between malignant melanoma and benign melanocytic nevi. Methods Archived nail apparatus melanomas were analyzed by fluorescence in situ hybridization (FISH) using probes targeting the genes at 6p25 (RREB1), 11q13 (CCND1), 8q24.1 (MYC), 6q23 (MYB), 9p21 (CDKN2A) and the centromeres of chromosomes 8 (D8Z2) and 6 (D6Z1). The results were correlated with clinical and demographic information. Results Mean patient age was 57.8 years (range 23-92 years). In all, 5 of 7 (71%) cases involved the upper extremity digits. RREB1 gain was seen in all cases. CCND1 gain was seen in 6 of 7 (86%) cases, 3 of which were amplified. MYB loss and MYC gain were both seen in 5 of 7 (71%) cases. Homozygous loss of CDKN2A was not observed in any case. Two of 7 (28.6%) patients had lymph node metastasis and died of widely metastatic disease. These 2 patients harbored the most genetic aberrations: gains of RREB1, CCND1, and MYC, and MYB loss. Both benign melanocytic nevi controls showed normal FISH results. Conclusions RREB1 and CCND1 gains are common in nail apparatus melanoma as in most melanomas, and an increased number of genetic aberrations may be associated with a poorer prognosis, though the limited number of cases precludes definitive correlation. FISH appears to be a useful adjunct in the diagnosis of nail apparatus melanomas and improves diagnostic confidence even in the setting of unambiguous histomorphology.
背景 甲襞恶性黑色素瘤极为罕见。越来越多的基因研究已被用于辅助鉴别恶性黑色素瘤和良性黑素细胞痣。方法 采用针对6p25（RREB1）、11q13（CCND1）、8q24.1（MYC）、6q23（MYB）、9p21（CDKN2A）基因以及8号（D8Z2）和6号（D6Z1）染色体着丝粒的探针，通过荧光原位杂交（FISH）对存档的甲襞黑色素瘤进行分析。将结果与临床和人口统计学信息相关联。结果 患者平均年龄为57.8岁（范围23 - 92岁）。总共7例中有5例（71%）累及上肢手指。所有病例均可见RREB1扩增。7例中有6例（86%）可见CCND1扩增，其中3例为高扩增。7例中有5例（71%）同时可见MYB缺失和MYC扩增。所有病例均未观察到CDKN2A纯合缺失。7例患者中有2例（28.6%）发生淋巴结转移并死于广泛转移的疾病。这2例患者存在最多的基因畸变：RREB1、CCND1和MYC扩增以及MYB缺失。两个良性黑素细胞痣对照的FISH结果均正常。结论 与大多数黑色素瘤一样，RREB1和CCND1扩增在甲襞黑色素瘤中很常见，基因畸变数量增加可能与预后较差相关，尽管病例数量有限，无法得出明确的相关性。FISH似乎是甲襞黑色素瘤诊断中的一种有用辅助手段，即使在组织形态学明确的情况下也能提高诊断信心。
